DESCRIPTION: (Applicant?s Abstract) The objective of this research proposal is to investigate the affect of exposure to delta-9 tetrahydrocannabinol on the immune response in mice to an infection within the central nervous system. The affect of four doses of THC on pathology within the brain will be examined when mice are infected with Acanthamoeba via hematoxylin and eosin staining. Differences in immune cell activation and recruitment will also be assessed using immunohistochemistry and monoclonal antibodies to specific surface markers. Alteration of transcription levels and protein production of inflammatory cytokines in response to THC treatment in infected mice will be determined using ribonuclease protection assays and ELISAs. FACS analysis will be performed using a dual staining technique in order to determine which types of cells are responsible for production of key cytokines. Each of the phases of this project will examine changes in responses of infected and uninfected mice using sequential sampling in order to determine the kinetics of the changes due to exposure to THC. Four doses of THC will be used in order to determine whether these changes are dose dependant. In this manner we plan to elucidate the immunomodulatory affects of THC for medical purposes or as a drug of abuse in regards to an extracellular CNS pathogen.